再生(生物学)
细胞生物学
巨噬细胞极化
巨噬细胞
神经损伤
细胞外基质
化学
下调和上调
M2巨噬细胞
周围神经损伤
生物
体外
神经科学
生物化学
基因
作者
Peiwen Chen,Matilde Cescon,Gaia Zuccolotto,Lucilla Nobbio,Cristina Colombelli,Monica Filaferro,Giovanni Vitale,M. Laura Feltri,Paolo Bonaldo
标识
DOI:10.1007/s00401-014-1369-9
摘要
Macrophages contribute to peripheral nerve regeneration and produce collagen VI, an extracellular matrix protein involved in nerve function. Here, we show that collagen VI is critical for macrophage migration and polarization during peripheral nerve regeneration. Nerve injury induces a robust upregulation of collagen VI, whereas lack of collagen VI in Col6a1(-/-) mice delays peripheral nerve regeneration. In vitro studies demonstrated that collagen VI promotes macrophage migration and polarization via AKT and PKA pathways. Col6a1(-/-) macrophages exhibit impaired migration abilities and reduced antiinflammatory (M2) phenotype polarization, but are prone to skewing toward the proinflammatory (M1) phenotype. In vivo, macrophage recruitment and M2 polarization are impaired in Col6a1(-/-) mice after nerve injury. The delayed nerve regeneration of Col6a1(-/-) mice is induced by macrophage deficits and rejuvenated by transplantation of wild-type bone marrow cells. These results identify collagen VI as a novel regulator for peripheral nerve regeneration by modulating macrophage function.
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